US3393211A - Naphthoquinone compounds - Google Patents

Naphthoquinone compounds Download PDF

Info

Publication number
US3393211A
US3393211A US487304A US48730465A US3393211A US 3393211 A US3393211 A US 3393211A US 487304 A US487304 A US 487304A US 48730465 A US48730465 A US 48730465A US 3393211 A US3393211 A US 3393211A
Authority
US
United States
Prior art keywords
naphthoquinone
hydroxy
propyl
ether
bromophenoxyphenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US487304A
Other languages
English (en)
Inventor
Michael H Fisher
Clarence S Rooney
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Priority to US487304A priority Critical patent/US3393211A/en
Priority to CH1281866A priority patent/CH472355A/de
Priority to GB39537/66A priority patent/GB1091810A/en
Priority to FR75233A priority patent/FR1509950A/fr
Priority to NL6612826A priority patent/NL6612826A/xx
Priority to BR182775/66A priority patent/BR6682775D0/pt
Priority to DE19661543771 priority patent/DE1543771A1/de
Application granted granted Critical
Publication of US3393211A publication Critical patent/US3393211A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C50/00—Quinones
    • C07C50/26—Quinones containing groups having oxygen atoms singly bound to carbon atoms
    • C07C50/32—Quinones containing groups having oxygen atoms singly bound to carbon atoms the quinoid structure being part of a condensed ring system having two rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C46/00—Preparation of quinones

Definitions

  • Anticoccidial 2 -hydroxy 3 [3 (4 phenoxyphenyl)- propyl] and 2 hydroxy 3 [3 (4 p halophenoxyphenyl)propyl]-1,4-naphthoquinones are prepared by reacting Z-hydroxy or 2,8-dihydroxy 1,4 naphthoquinone with a butyryl peroxide substituted in the 4-position with a phenoxyphenyl or halophenoxyphenyl radical. It is contemplated that dosage units of these active compounds will be administered orally in the control of coccidiosis in poultry.
  • This invention relates to novel chemical compounds, and to the chemical synthesis of such compounds. More particularly, it relates to 2-hydroxy-3-substituted propyl 1,4-naphthoquinones, to the preparattion thereof, and to the use of these novel naphthoquinones against the poultry disease coccidiosis.
  • the compounds of this invention may be represented by the structural formula:
  • Y O H Y represents hydrogen or hydroxy
  • X represents hydrogen or halo, preferably bromo or chloro, where in any given compound one of X and Y is always other than hydrogen. In the preferred compounds of the invention, one of X and Y is hydrogen while the other is not.
  • novel compounds described above are prepared by reacting 2-hydroxy-1,4- naphthoquinone or 2,8-dihydroxy-1,4-naphthoquinone (I) with an alkylating agent which is a butyryl peroxide substituted in the 4-position with a phenoxyphenyl or halophenoxyphenyl radical, as illustrated in the fiow diagram:
  • Examples of compounds provided according to this process by reaction of the appropriately substituted 1,4- naphthoquinone and butyryl peroxide are 2-hydroxy-3 [3- 4-p-bromophenoxyphenyl -propyl 1,4-naphthoquinone;
  • novel compounds provide-d by this invention are active against poultry coccidiosis and are thus useful in the prevention and treatment of this parasitic disease when orally administered to poultry susceptible to it.
  • they may be given in the feedstufi of the birds, in the drinking water, or if desired by direct administration dissolved or suspended in a suitable solvent. In any case, only minor amounts are required in order to obtain the desired anticoccidial result.
  • These substances are useful in particular against coccidiosis due to the organism Ez'meria brunetti, one of the species that is responsible for the so-called intestinal form of coccidiosis.
  • feed concentrations of from about 0.0075% to about 0.05% by weight (of naphthoquinone in feed) are usually employed, with dose levels of about 0.01% to 0.03% being preferred. It might be mentioned here that dose levels of poultry coccidiostats are expressed in the art in terms of percent concentration of drug in the feed or drinking water because the exact amount of feed or water con- 3 sumed by an individual bird is not measured as a matter of general practice.
  • the feedstutf compositions referred to above are those normally used in the poultry-raising industry. They may be so-called mashes containing ground grain, protein, and mineral and vitamin concentrates. Alternatively, they may consist of broiler feeds made up primarily of corn together with proteins and growth factors. In any event, the feedstulfs supplemented with the coccidiostats of this invention vare nutritionally adequate ones for the poultry.
  • the anticoccidial compositions of the invention may contain one or more other coccidiostats in addition to the 3-substituted-2-hydroxy-1,4-naphthoquinones of Formula III above, and in many instances such combinations are preferred by the poultry grower.
  • butyryl peroxides of Formula II above used as one of the reactants in the process of this invention are prepared from the corresponding butyryl chlorides by reaction of said latter substance with hydrogen peroxide. This method is described in some detail in Example 1.
  • Example 1 A mixture of 50.3 g. (0.15 m.) of 4-(4-p-bromophenoxyphenyl)butyric acid and 20 ml. of thionyl chloride in 150 ml. of chloroform is heated for two hours on a steam bath. The mixture is then evaporated to dryness to give a residue of 4-(4-p-bromophenoxyphenyl)butyryl chloride. This acid chloride is dissolved in 200 m1. of ether at C., and 10.8 ml. of 30% hydrogen peroxide added dropwise to the cold ether solution. 8.85 gm. of sodium hydroxide in 20 ml. of water is cooled to 5 C.
  • the methanol solution is concentrated to dryness and the residue thus obtained combined with methanolinsoluble material obtained from the ether concentration.
  • the combined residues are crystallized from benzenepetroleum ether (30-60 C.) to give 2-hydroxy-3[3-(4-pbromophenoxyphenyl)propyl] 1,4-naphthoquinone, M.P. 113-114 C. Recrystallization from absolute ethanol aflords substantially pure material, M.P. 116-117" C.
  • the 4-(4 p bromophenoxyphenyl)butyric acid employed as starting material in the above procedure is prepared from 3-(4-p-bromophenoxy)benzoyl .propionic acid by reacting 120 gm. of said acid with 50 ml. of hydrazine hydrate and gm. of potassium hydroxide in 500 ml. of triethylene glycol according to the method of Huang- Minlon, J. Am. Chem. Soc. 68, 2487 .(1946).
  • Example 2 6.3 gm. (0.033 m.) of 2,84lihydroxy-1,4-naphthoquinone and 21 g. (0.036 m.) of 4-(4-phenoxyphenyl) butyryl peroxide is added to ml. of glacial acetic acid, and the resulting mixture heated on a steam bath for two hours. The mixture is then concentrated to dryness in vacuo and the residue dissolved in about 700 ml. of diethyl ether. The ethereal solution is extracted with 600 ml. portions of saturated aqueous sodium bicarbonate until the aqueous extracts become essentially colorless. The ether solution is then washed with about 50 ml.
  • -OH where X is hydrogen, chloro or brorno, Y is hydrogen or hydroxy, and one of X and Y is other than hydrogen.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Fodder In General (AREA)
US487304A 1965-09-14 1965-09-14 Naphthoquinone compounds Expired - Lifetime US3393211A (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
US487304A US3393211A (en) 1965-09-14 1965-09-14 Naphthoquinone compounds
CH1281866A CH472355A (de) 1965-09-14 1966-09-05 Verfahren zur Herstellung von Naphthochinonen
GB39537/66A GB1091810A (en) 1965-09-14 1966-09-05 Naphthoquinone derivatives
FR75233A FR1509950A (fr) 1965-09-14 1966-09-05 Production de nouvelles 1, 4-naphtoquinones substituées
NL6612826A NL6612826A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1965-09-14 1966-09-12
BR182775/66A BR6682775D0 (pt) 1965-09-14 1966-09-12 Processo para preparar novas 2-hidroxi-3-substituido propil 1,4-naftoquinonas
DE19661543771 DE1543771A1 (de) 1965-09-14 1966-09-13 2-Hydroxy-3-subst.-propyl-1,4'-naphthochinone und Verfahren zu deren Herstellung

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US487304A US3393211A (en) 1965-09-14 1965-09-14 Naphthoquinone compounds

Publications (1)

Publication Number Publication Date
US3393211A true US3393211A (en) 1968-07-16

Family

ID=23935197

Family Applications (1)

Application Number Title Priority Date Filing Date
US487304A Expired - Lifetime US3393211A (en) 1965-09-14 1965-09-14 Naphthoquinone compounds

Country Status (7)

Country Link
US (1) US3393211A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
BR (1) BR6682775D0 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
CH (1) CH472355A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
DE (1) DE1543771A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
FR (1) FR1509950A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
GB (1) GB1091810A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
NL (1) NL6612826A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4485116A (en) * 1981-10-16 1984-11-27 Hudson Alan T Antiprotozoal compounds
US4485117A (en) * 1981-10-16 1984-11-27 Hudson Alan T Antiprotozoal compounds

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2159056A (en) * 1984-04-04 1985-11-27 Alan Alaexander Torrance Sime Biocidal compositions comprising polyhydroxynaphthoquinones
DE102005054989B4 (de) * 2005-11-16 2022-09-08 Kabe-Labortechnik Gmbh Blutentnahmevorrichtung

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4485116A (en) * 1981-10-16 1984-11-27 Hudson Alan T Antiprotozoal compounds
US4485117A (en) * 1981-10-16 1984-11-27 Hudson Alan T Antiprotozoal compounds

Also Published As

Publication number Publication date
DE1543771A1 (de) 1969-11-27
BR6682775D0 (pt) 1973-10-25
FR1509950A (fr) 1968-01-19
NL6612826A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1967-03-15
GB1091810A (en) 1967-11-22
CH472355A (de) 1969-05-15

Similar Documents

Publication Publication Date Title
US3652646A (en) Carboxylic acid derivatives
JPS60248656A (ja) ジアリ−ル化合物の製造方法
White et al. The Metabolism of 2, 2 Bis (P-Chlorophenyl) 1, 1, 1 Trichloroethane (DDT). I. A Metabolite from Rabbit Urine, Di (P-Chlorophenyl) acetic Acid; Its Isolation, Identification, and Synthesis
JPS59104346A (ja) ナフタレン抗乾癬剤
US3393211A (en) Naphthoquinone compounds
US3873620A (en) Phenoxyalkylamines, process for their preparation and applications thereof
US2562208A (en) Fungistatic composition
US3255242A (en) (alpha-alkylideneacyl)naphthyloxy monocarboxylic acids
DE2737738A1 (de) Derivate der 3-minothiophen-4-carbonsaeure, herstellungsverfahren und mittel cyclische verbindungen
Tullar et al. Esters of N-tert-butylarterenol. Long-acting new bronchodilators with reduced cardiac effects
US3132176A (en) Preparation of o, o-dialkanoyl derivatives of d, l-alpha-alkyl-beta-3, 4-dihydroxyphenylalanine by preferential acylation
US2483381A (en) Beta-dihydro-inylamine and the acid addition salts thereof
JPS60185745A (ja) 抗乾癬性ナフタレン化合物
US2179979A (en) alpha-naphthacetyl-amino acids and process for the manufacture of same
SU1591808A3 (ru) Способ получения замещенных 3-фенил-7н-тиазпло[3,2-ъ] [1,2,4]'· триазин-7-онов и способ получения 2-амино-6н-1,3,4-тиадиазинов
US2691039A (en) Stilbene-alpha-ketol compounds and process for making the same
US3287396A (en) Phenyldesoxythyronines
US3551491A (en) 4 - halothymyl - (n - ethyl - n - beta - chloroethyl - 1- and-2 - amino propyl(2) and (1)) ether and salts thereof
Weizmann et al. β, β-Diarylacrylic Acids. III. Esters with Diethylaminoethanol as Anesthetics
DE929551C (de) Verfahren zur Herstellung neuer Vitamin-B-Abkoemmlinge
US3838173A (en) 2-nitro-5 or 6 or 7-methoxy benzofuran
US3448141A (en) Unsymmetrical derivatives of djenkolic acid
US2430006A (en) 4-methyl-5-imidazolone-(2)-caproic acid and esters thereof
US3201475A (en) Bisglyoxalyldiphenyl derivatives
US2938925A (en) 2-(alpha-naphthyl)-1, 3-diketohydrindene